Peperomia pellucida (L.) Kunth suppresses glycation‐induced inflammatory response in human retinal pigment epithelial cell line ARPE‐19 via JAK‐STAT3 signaling

Abstract

AbstractThe formation of advanced glycation end product (AGE) is a risk factor for diabetic retinopathy. Since the current treatment for diabetic retinopathy is accompanied by side effects, preliminary findings have suggested Peperomia pellucida (L.) Kunth as a potential alternative therapeutic option for diabetic retinopathy. This study aimed to elucidate the anti‐inflammatory mechanism of P. pellucida in the AGE‐stimulated human retinal pigment epithelial cell line ARPE‐19. Phytochemical analysis revealed phenylpronanoids, terpenes, and fatty acids in P. pellucida. Through in vitro cell viability assay, the P. pellucida methanolic extract (IC50 = 8.70 mg/mL) and ethyl acetate fraction (IC50 = 7.34 mg/mL) were considered as non toxic for ARPE‐19. AGE induced an inflammatory response in ARPE‐19 by upregulating the gene (2.4–5.8‐fold) and protein (1.4–2.3‐fold) expression of signal transducer and activator of transcription 3 (STAT3), interleukin‐8 (IL‐8), monocyte chemoattractant protein‐1, matrix metalloproteinase 2, and vascular endothelial growth factor. At 1.5 mg/mL, P. pellucida methanolic extract suppressed IL‐8 expression (p < 0.05), implying its anti‐inflammatory action at the early inflammatory stage through the Janus kinase (JAK)‐STAT3 pathway. The methanolic extract also restored the ARPE‐19 viability under AGE‐induced inflammatory stress. The downregulation of inflammatory biomarkers along the JAK‐STAT3 pathway suggested P. pellucida as a promising anti‐inflammatory source for diabetic retinopathy.